title: CXCL10 blockade protects mice from cyclophosphamide-induced cystitis.
abstract: BACKGROUND
  Alterations in serum CXCR3 ligand levels were examined in interstitial cystitis (IC) patients; similar expression patterns in serum as well as CXCR3, CXCR3 ligands, and cytokines expressed by peripheral and local leukocyte subpopulations were characterized during cyclophosphamide (CYP)-induced acute cystitis in mice.
  
  
  RESULTS
  Serum levels of monokine-induced by interferon-gamma (IFN-gamma) (MIG/CXCL9), IFN-gamma-inducible protein-10 (IP-10/CXCL10), and IFN-gamma-inducible T cell alpha chemoattractant (I-TAC/CXCL11) were elevated in patients with IC. These clinical features closely correlated with CYP-induced cystitis in mice. Serum levels of these CXCR3 ligands and local T helper type 1 (Th1) cytokines were also increased. We demonstrate that CXCR3 as well as CXCL9, CXCL10 and CXCL11 mRNA were significantly expressed by urinary bladder lymphocytes, while CXCR3 and CXCL9 transcripts were significantly expressed by iliac lymph node leukocytes following CYP treatment. We also show that the number of CD4+ T cells, mast cells, natural killer (NK) cells, and NKT cells were increased at systemic (spleen) and mucosal (urinary bladder and iliac lymph nodes) sites, following CYP-induced cystitis in mice. Importantly, CXCL10 blockade attenuated these increases caused by CYP.
  
  
  CONCLUSIONS
  Antibody (Ab)-mediated inhibition of the most abundant serum CXCR3 ligand, CXCL10, in mice decreased the local production of CXCR3 ligands as well as Th1 cytokines expressed by local leukocytes, and lowered corresponding serum levels to reduce the severity of CYP-induced cystitis. The present study is among the first to demonstrate some of the cellular and molecular mechanisms of chemokines in cystitis and may represent new drug target for this disease.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Senthilkumar K
authors.initials: SK
authors.lastname: Sakthivel
authors.affiliation: Deparment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Udai P
authors.initials: UP
authors.lastname: Singh
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
authors.forename: Shailesh
authors.initials: S
authors.lastname: Singh
authors.affiliation: Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Taub
authors.affiliation: Department of Urology, University of Louisville, Louisville, KY, USA.
authors.forename: Kristian R
authors.initials: KR
authors.lastname: Novakovic
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.|Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Lillard